{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T14:06:24Z","timestamp":1793023584692,"version":"4.5.0"},"reference-count":47,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["DK108868,DK110845,DK032083,DK099317,DK032493,DK116073"],"award-info":[{"award-number":["DK108868,DK110845,DK032083,DK099317,DK032493,DK116073"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Juvenile Diabetes Research Foundation","award":["3-PDF-2020-943-A-N"],"award-info":[{"award-number":["3-PDF-2020-943-A-N"]}]},{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"crossref","award":["2103-05093"],"award-info":[{"award-number":["2103-05093"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011866","name":"Colorado Clinical and Translational Sciences Institute","doi-asserted-by":"crossref","award":["TR002535"],"award-info":[{"award-number":["TR002535"]}],"id":[{"id":"10.13039\/100011866","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,22]]},"abstract":"<jats:p>\n                    T cell receptor (TCR) sequences are exceptionally diverse and can now be comprehensively measured with next-generation sequencing technologies. However, a thorough investigation of longitudinal TCR repertoires throughout childhood in health and during development of a common childhood disease, type 1 diabetes (T1D), has not been undertaken. Here, we deep sequenced the TCR-\u03b2 chain repertoires from longitudinal peripheral blood DNA samples at 4 time points beginning early in life (median age of 1.4 years) from children who progressed to T1D (\n                    <jats:italic>n =<\/jats:italic>\n                    29) and age\/sex-matched islet autoantibody-negative controls (\n                    <jats:italic>n =<\/jats:italic>\n                    25). From 53 million TCR-\u03b2 sequences, we show that the repertoire is extraordinarily diverse early in life and narrows with age independently of disease. We demonstrate the ability to identify specific TCR sequences, including those known to recognize influenza A and, separately, those specific for insulin and its precursor, preproinsulin. Insulin-reactive TCR-\u03b2 sequences were more common and frequent in number as the disease progressed in those who developed T1D compared with genetically at risk nondiabetic children, and this was not the case for influenza-reactive sequences. As an independent validation, we sequenced and analyzed TCR-\u03b2 repertoires from a cohort of new-onset T1D patients (\n                    <jats:italic>n =<\/jats:italic>\n                    143), identifying the same preproinsulin-reactive TCRs. These results demonstrate an enrichment of preproinsulin-reactive TCR sequences during the progression to T1D, highlighting the importance of using disease-relevant TCR sequences as powerful biomarkers in autoimmune disorders.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.161885","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T12:00:27Z","timestamp":1661256027000},"source":"Crossref","is-referenced-by-count":33,"title":["Temporal development of T cell receptor repertoires during childhood in health and disease"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1955-5850","authenticated-orcid":true,"given":"Angela M.","family":"Mitchell","sequence":"first","affiliation":[{"name":"Barbara Davis Center for Diabetes and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8936-434X","authenticated-orcid":true,"given":"Erin E.","family":"Baschal","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen A.","family":"McDaniel","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7169-8077","authenticated-orcid":true,"given":"Kimber M.","family":"Simmons","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes and"},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pyle","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes and"},{"name":"Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Waugh","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea K.","family":"Steck","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes and"},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Yu","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes and"},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA."},{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3829-9207","authenticated-orcid":true,"given":"Marian J.","family":"Rewers","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes and"},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA."},{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes and"},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA."},{"name":"Department of Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-5244","authenticated-orcid":true,"given":"Aaron W.","family":"Michels","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes and"},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA."},{"name":"Department of Medicine and"},{"name":"Department of Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-407707-2.00001-1","article-title":"The interdisciplinary science of T-cell recognition","volume":"119","author":"Huppa","year":"2013","journal-title":"Adv 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